Estrogenic activity of glycitein, a soy isoflavone

Tong T. Song, S. Hendrich and P.A. Murphy, J.Agric. Food Chem., 47,1607-1610, 1999.

In most soy foods, genistein and daidzein account for about 80 – 90% of total isoflavones. In soy germ, the major isoflavones present are daidzein (45-60%) and glycitein (35-45%). In studies, the estrogenic activities of genistein and daidzein were reported to be about 100,000 to 500,000 times lower than that of diethylstilbestrol (DES). In this study, the estrogenic activity of glycitein was assessed, using SoyLife, a soy germ concentrate.

Study design

Two different tests were applied to test the estrogenic activity of glycitein. In the first test, purified isoflavones were tested in an in vitro estrogen receptor-binding assay. The second test involves a uterine enlargement test with B6D2F1 mice. This is a standard in vivo method to evaluate estrogenic activity. Because it is performed in animals, the effects of absorption, metabolism, serum binding and pharmacokinetics are taken into account. Eighty mice were randomly assigned to a 4-day treatment involving a placebo, to 0.12 ?g DES per day, or to 12 mg per day of either genistein or glycitein. Glycitein was purified from SoyLife. The relative estrogenic potencies were estimated on the basis of the doses required to produce the same increase of uterine weights.


The study demonstrated that the estrogenic potency of glycitein (as measured in the mice uterine enlargement assay) was in the same order, although somewhat higher than that of genistein. But, as hypothesized, the estrogenic potency of both isoflavones was much lower than that of DES or 17?-estradiol.

It is generally believed that non-steroidal estrogens such as isoflavones exert an estrogenic effect by binding to the same estrogen receptors as steroidal estrogens such as 17?-estradiol. Our study confirms that glycitein has the ability to bind to estrogen receptors.

However, among the three isoflavones, genistein had the greatest estrogen receptor binding affinity (as demonstrated in the in vitro ER-binding essay.

In conclusion

This study demonstrates that glycitein is a slightly stronger estrogen in vivo in mice compared to genistein, although the estrogenic activity of both compounds is much weaker than that of DES or 17?-estradiol. Contradictory, genistein was shown to have higher ER-binding affinity than glycitein in vitro. The somewhat higher in vivo estrogenic activity of glycitein compared to genistein may be a result of a higher bioavailability of glycitein. Further, the authors suggest that glycitein might be metabolized to other compounds, which have a greater estrogenic potency than that of glycitein. These metabolites were however not measured in this study.